Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

Abstract

Epidemiological studies have revealed striking associations between several distinct behavioral/personality traits and drug addiction, with a large emphasis on the sensation-seeking trait and the associated impulsive dimension of personality. However, in human studies, it is difficult to identify whether personality/behavioral traits actually contribute to increased vulnerability to drug addiction or reflect psychobiological adaptations to chronic drug exposure. Here we show how animal models, including the first multi-symptomatic model of addiction in the rat, have contributed to a better understanding of the relationships between different subdimensions of the sensation-seeking trait and different stages of the development of cocaine addiction, from vulnerability to initiation of cocaine self-administration to the transition to compulsive drug intake. We argue that sensation seeking predicts vulnerability to use cocaine, whereas novelty seeking, akin to high impulsivity, predicts instead vulnerability to shift from controlled to compulsive cocaine use, that is, addiction.

Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring

“…Since increased decision-making and risk assessment behaviors were related with the modulation of dopamine levels in the mesolimbic system, which leads to a higher vulnerability to drug addiction [15,43,62,81,111,118], in the present study we tested the hypothesis that maternal nicotine exposure during lactation is associated with changes in the dopaminergic and opioid signaling pathways in the brain reward system of the adult offspring, and that these alterations are associated with changes in the offspring's food preference and behavior.…”

High Locomotor Reactivity to Novelty Is Associated with an Increased Propensity to Choose Saccharin Over Cocaine: New Insights into the Vulnerability to Addiction

“…After 17 days of self-administration, motivation for the drug was tested in a progressive ratio schedule of reinforcement (Belin and Deroche-Gamonet, 2012). During this session, drug availability was signalled by the illumination of the chamber.…”

“…The self-administration procedure has been previously described (Belin et al, 2009;Belin and Deroche-Gamonet, 2012). After the discrete-trial choice procedure, rats underwent daily selfadministration (SA) sessions composed of three drug components (40 min each) signalled by the house light on and separated by 15 min of drug-free periods signalled by the house light switched off.…”

“…However, vulnerability to addiction is a multifaceted construct, Belin and Deroche-Gamonet, 2012) with several factors contributing differentially to the distinct stages of drug use that ultimately leads to addiction. These range from the individual propensity to use drugs to the increased motivation toward the drug and eventually the loss of control over drug intake that becomes compulsive.…”

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

“…Selectively bred high-responder (bHR) rats exhibit high levels of activity in response to novelty and bred low-responder (bLR) rats exhibit low levels of activity (Stead et al 2006). Although these rats are bred based on locomotor response to novelty, we seem to have co-selected for several traits in the bred lines that are not necessarily apparent in outbred high- and low-responder rats (see Flagel et al 2014; Belin et al 2008, 2011; Belin and Deroche-Gamonet 2012). While bHR rats exhibit a number of addiction-related traits, including increased aggression and impulsivity, bLR rats are more anxious and more reactive to stress (see Flagel et al 2014).…”